Moss - What genes cant do - 2003, страница 13

. . Cytoplasm is perhaps more prone to “memory,” Jollos’sexperiments with Infusoria for instance seem to suggest such a case (Johannsen1923).42Chapter 1Johannsen reproduces in these remarks the central distinction he wishesto make between the genotype and phenotype. The genotype, taken asa whole, confers an ahistorical potential for a full range of phenotypeswhere the phenotype reflects the genotype in the context of the ongoingresult of cumulative experience.

The chromosomes, which clearly standin a special relationship to the genotype, undergo a kind of “rejuvenescence” during gametogenesis, which serves to wipe the slate clean of historical experience. The cytoplasm, by contrast, appears to be capableof responding to the conditions of lived existence and of retaining thelessons of experience as a kind of memory. In the case of the Jollos experiments that Johannsen refers to, it was found that protozoa exposed toextreme conditions may undergo physiological adaptations and retainsuch adaptations for many generations in the absence of those conditions. Ultimately the protozoa were found to be capable of reverting backto the nonadapted state.

In as much as the protozoa appeared to adaptand revert on a population-wide basis and not on the basis of the clonalselection and expansion of a mutant cell, the phenomenon displayed thecharacter of an epigenetic cellular memory. Johannsen’s ascription ofmemory to the cytoplasm, prompted it appears by Jollos’s work, recallsboth Morgan’s earlier emphasis on the role of the cytoplasm in ontogenetic differentiation and development, as well as that of Driesch, Boveri,Whitman, and Conklin on the role of the cytoplasm in setting up themore generic properties of the organism. It should also be noted that thequestion of the rejuvenescence of the chromosome derived from differentiated cells is exactly the central technical challenge of human animalcloning, and especially in light of recent revelations of the widespreaddifficulties in producing healthy animals through such means,14 it is aquestion in relation to which the jury is still out.Johannsen’s demarcation of the genotype from the phenotype providedthe conceptual groundwork for Morgan to use phenotypic features asmarkers for underlying genotypic realities.

In so doing he could evadethe pitfalls of the morphological tradition, i.e., of the reductionistic preformationism with which Morgan would have no truck. In the practiceof instrumental reductionism, genes are not construed as particles of thephenotype; rather, aspects of the phenotype are used as markers of genesas if they were directly determined by genes in order to provide theGenesis of the Gene43window needed to develop a science of the genotype. Classical geneticsenjoyed its formative stage in Morgan’s Fly Room where genes materialized as alleles at chromosomal loci which could be mapped with respectto their chromosomal address and linkage neighborhood.

However, inthe wake of the fruits of the instrumentalist program, the clarity obtainedin Johannsen’s reflections—the conceptual high-water mark of the classical gene concept—quickly became muddied.Johannsen’s model made possible, not only a productive applicationof instrumental reductionism, but also, and inseparably, a lens withwhich to resolve its meaning.The necessary complement to the instrumental preformationismafforded by Johannsen is, I will argue, an epigenesist research programwith which to reveal its biological meaning.

Following Johannsen’svision, the genotype as a whole confers the potential for a wide rangeof phenotypes with an ability to adapt to the needs of the particularcircumstances of existence. The immediate context that determines theway in which the potential of the genotype is realized is the organizational structure of the cell-organism—which we can now envisage atthe level of chromosomal, membrane, cellular, supercellular organization, and metabolic dynamics—indeed, all that lies beyond the onedimensional array of coding nucleic acid sequences. And the cytoplasmof the organism, as inferred by Driesch and his holistic successors, isimmediately responsive to the larger environment.

Now, the chromosomes, as Johannsen anticipated, may well undergo a form of rejuvenescence, but the cytoplasm of the egg is, as Whitman, Conklin, andLillie held, a very likely candidate for retaining historical (generic?species?) memory. Johannsen’s instrumental reductionism and genotypeconcept require that the genotype at birth is conceived independentlyof any cytoplasmic historical memory.

But given the holistic natureand pluralistic potential of Johannsen’s genotype, the achievement of thephenotype must be the result of an epigenesis within which chromosomal, cytoplasmic, and environmental constituents become mutually andreciprocally causal, instructive, and determinative of the outcome. Ironically, as the means for elucidating the ahistorical chemical features ofthe genotype emerged, that embryological tradition that was bestequipped to provide the necessary complement for elucidating the44Chapter 1context-specific interactions which actually produce a phenotype becameincreasingly marginalized.Information by ConflationThe insights that allowed genetics to emerge as an independent disciplineincluded insight into its own limitations.

But the victory of genetics insecuring the mantle of heredity for its sole possession (Sapp 1987) leftlittle room for humility, conceptual or otherwise. The self-understandingof Johannsen’s genetics, i.e., as that of an instrumental reductionism,gave way to a less-reflective disciplinary juggernaut. If geneticists werenot going to pursue the biology of the phenotype by way of a theory ofepigenesis, the alternative, other than a return to old-fashioned morphological preformationism, would have to be along the lines of a newpreformationism that locates within the gene its own instructions for use.The idiom, if not the substance, for describing this was soon found inthe jargon of “codes and information” which began to surface in the1940s but hit pay dirt after the Watson and Crick breakthrough in 1953.Molecular genetics emerged as essentially that science that wouldexplain, in physiochemical terms, how the genotype contains within itselfthe instructions for making an organism.

Its recruits arrived largely fromthe shores of physics and chemistry and included among its ranks manyfor whom even a current knowledge of the cell was more biology thandeemed necessary for the putatively information–encryption-theoretictask at hand.The rhetoric of the gene as code and information, so familiar now asto resemble common sense, turns on, I will argue, a conflation of twodistinctly different meanings of the gene. When scientists and cliniciansspeak of genes for breast cancer, genes for cystic fibrosis, or genes forblue eyes, they are referring to a sense of the gene defined by its relationship to a phenotype (i.e., the characteristics of the person or organism) and not to a molecular sequence.

The condition for having a genefor blue eyes or a gene for cystic fibrosis does not entail having a specific nucleic acid (DNA) sequence but rather an ability to predict, withincertain contextual limits, the likelihood of some phenotypic trait. Whatmolecular studies have revealed is that these phenotypic differences areGenesis of the Gene45not due to the presence of two qualitatively different capabilities, butrather the absence of the ability to make the so-called normal protein.Accordingly, there is no specific structure for the gene for white flowersor the gene for blue eyes or the gene for many diseases because there aremany structural ways to be lacking the usual resource.

The white flower,the blue eye, the albino skin, the cystic fibrosis lung are all the highlycomplex results of what an organism will do in the absence of certainnormal molecular structures.It continues to be useful, in some contexts, to employ this usage of theword “gene.” To speak of a gene for a phenotype is to speak as if, butonly as if, it directly determines the phenotype. It is a form of preformationism but one deployed for the sake of instrumental utility. I callthis sense of the gene—Gene-P, with the P for preformationist (seeFigure 1.2). Genes for phenotypes, i.e., Genes-P, can be found, generally—and as Johanssen surmised—where some deviation from a normalsequence results with some predictability in a phenotypic difference.15In the absence of the normal sequence necessary for making brown eyepigment, blue eye color results. Any absence of this brown eye–makingresource will thus count as a gene for blue eyes.

Blue eyes are not madeaccording to the directions of the Gene-P for blue eyes rather blue eyesare the result of what organisms do in the absence of the brown eyepigment. Reference to the gene for blue eyes serves as a kind of instrumental short hand with some predictive utility.Thus far Gene-P sounds purely classical, that is, Mendelian as opposedto molecular. But a molecular entity can be treated as a Gene-P as well.BRCA1, the gene for breast cancer, is a Gene-P, as is the gene for cysticfibrosis, even though in both cases phenotypic probabilities based onpedigrees have become supplanted by probabilities based on molecularprobes. What these molecular probes do is to verify that some normalDNA sequence is absent by confirming the presence of one, out of manypossible, deviations from that normal sequence that has been shown tobe correlated (to a greater or lesser extent) with some phenotypic abnormality. To satisfy the conditions of being a gene for breast cancer or agene for cystic fibrosis does not entail knowledge about the biology ofhealthy breasts or of healthy pulmonary function, nor is it contingentupon an ability to track the causal pathway from the absence of the46Chapter 1normal sequence resource to the complex phenomenology of these diseases.